crossing96/oncoscreening huggingface dataset:
A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model.	PURPOSE: The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research. PROCEDURE: The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination. RESULTS: Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals. CONCLUSIONS: Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.	bladder
A Functional rs353293 Polymorphism in the Promoter of miR-143/145 Is Associated with a Reduced Risk of Bladder Cancer.	BACKGROUND AND OBJECTIVES: MicroRNA (miR)-143/145, known as tumor suppressors, can promote cell apoptosis and differentiation, and suppress cell proliferation, invasion and migration. We performed a case-control study to investigate the association of rs353293 in the promoter region of miR-143/145 with bladder cancer risk. METHODS: In total, 869 subjects including 333 cases and 536 controls were enrolled in this study, and the rs353293 polymorphism was genotyped by using a Taqman assay. The promoter activity was measured by the Dual-Luciferase Assay System. RESULTS: We calculated an adjusted odds ratio of 0.64 for the presence of either AA/AG genotypes (95% CI 0.46-0.90) and 0.64 (95% CI 0.47-0.87) for carrying at least one A allele in bladder cancer. Stratified analyses showed that the AA/AG genotypes and the A allele were less prevalent in patients with low grade tumors, compared to those harboring higher grade bladder cancers (adjusted OR = 0.53, 95% CI, 0.30-0.94, P = 0.03 and adjusted OR = 0.54, 95% CI, 0.32-0.92, P = 0.02, respectively). In vitro luciferase reporter analysis showed that rs353293A allele had a lower activity compared with the rs353293G allele (P < 0.001). CONCLUSION: These findings suggest that the functional rs353293 polymorphism may be a useful biomarker to predict the risk of bladder cancer.	bladder
Effect of autophagy on cisplatin-induced bladder cancer cell apoptosis.	BACKGROUND: To investigate the effects of autophagy in cisplatin-induced apoptosis of bladder cancer cells. METHODS: Bladder cancer cell T24 was regarded as cell model. The transmission electron microscope was employed to detect autophagic vacuoles and the fluorescence microscope to detect the fluorescence accumulation profile of vectors for green fluorescent protein and microtubule associated protein 1 light chain 3 fusion protein (GFP-LC3). Protein immunoblotting was applied to detect the accumulation of LC3-II, thus detecting whether cisplatin could induce the bladder cancer T24 cell autophagy. Moreover, protein immunoblotting was ultilized to detect the autophagic relative signal pathway mammal target of rapamycin (mTOR) and the variation of ribosomal protein S6 kinase (P70S6K) with relative molecular mass 70,000 in downstream as well as the cleavage of apoptosis marker protein poly ADP-ribose polymerase (PARP). Afterwards, with the utilization of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS), the viability changes in cisplatin-induced bladder cancer cells under the condition of autophagy promoting the presentation or absence of rapamycin were observed. Moreover, RNA interference was also adopted in this experiment to knockdown the LC3 expression. RESULTS: Compared with the control group, the electron microscope revealed that cisplatin was able to induce plenty of autophagic vacuoles in bladder cancer cells. CFP-LC3 aggregation was viewed by the fluorescence microscope, showing a significant higher in cisplatin group than control group. The results of LC3 detected by protein immunoblotting indicated that the LC3-II content in cisplatin group was significantly enhanced with the prolongation of time and increase of cisplatin concentration. Especially, at the concentration of 50 and 100 μmol/L for 48 hours with cisplatin treatment, the gray value of LC3-II/Actin (%) increased 30 and 44, respectively. Cisplatin treatment inhibited the phosphorylation of mTOR/P70S6K, and its phosphorylated strips were almost completely inhibited in the 100 μmol/L for 48 hours with cisplatin treatment. MTS results showed that cisplatin was able to lead to the loss of cell viability, which was 12% and 35% at the concentration of 50 μmol/L, and 100 μmol/L for 24 hours with cisplatin treatment. Moreover, the cell viability loss in autophagy-induced rapamycin and cisplatin combined treatment group was bigger than that with single-use cisplatin treatment in control group (F=74.890, P<0.01). Besides, RNA interference experiment revealed that knocking down autophagic relative gene LC3 could reduce the PARP cleavage induced by cisplatin and the apoptosis was decreased. CONCLUSIONS: Cisplatin could induce autophagy in bladder cancer cell T24, which promoted cisplatin-induced apoptosis.	bladder
Preoperative Imaging for Clinical Staging Prior to Radical Cystectomy.	The importance of patient selection for quality outcomes following radical cystectomy is critical. Clinical staging is one of the key elements necessary for patient selection, and staging relies on accurate preoperative imaging. Many imaging modalities are available and have been utilized for preoperative staging with published operating characteristics. In this update, we review recently published literature for advances in preoperative imaging prior to radical cystectomy.	bladder
Comparison of the morbidity and mortality of cystectomy and ileal conduit urinary diversion for neurogenic lower urinary tract dysfunction according to the approach: Laparotomy, laparoscopy or robotic.	OBJECTIVES: To evaluate and compare the morbidity and mortality of cystectomy-ileal conduit urinary diversion in patients with neurogenic lower urinary tract dysfunction according to the surgical approach, and to evaluate predictive factors of early and late morbidity. METHODS: This was a single-center retrospective study based on 65 patients operated between May 2005 and December 2011. The surgical approach consisted of: laparotomy (n = 11), laparoscopy (n = 14) and robotic (n = 40). Evaluation of early (<30 days) and late (>30 days) morbidity and mortality was carried out according to the Clavien-Dindo classification. RESULTS: The operating time was longer (P = 0.007) and the mean time to return of bowel function was shorter (P = 0.012) in the robotic group. The early complication rate for the overall population was 41.5%: minor complications in 32.3% of cases and major complications in 9.2% of cases. A tendency towards a lower minor complication rate was observed in favor of robotic surgery (P = 0.08), with a reduction of the postoperative hemorrhagic complication rate (P = 0.03). The late complication rate for the overall population was 43.1%: minor complications in 20% and major complications in 23.1%. A lower surgical revision rate under general anesthesia was observed in favor of robotic surgery (P = 0.03). No predictive factor of early and late morbidity was identified. CONCLUSION: Robotic cystectomy-ileal conduit urinary diversion in patients with neurogenic lower urinary tract dysfunction is feasible and safe. Its morbidity in experienced hands seems to be limited and comparable with laparoscopy or open surgery.	bladder
Carbon-ion radiotherapy for locally advanced cervical cancer with bladder invasion.	The purpose of this study was to evaluate the efficacy and toxicities of carbon-ion radiotherapy (C-ion RT) for locally advanced cervical cancer with bladder invasion by a subset analysis of pooled data from eight prospective clinical trials at the National Institute of Radiological Sciences. Between June 1995 and January 2014, 29 patients with locally advanced cervical cancer with bladder invasion were identified. The median age was 56 years old (range 31-79 years old). The median tumor size at diagnosis on magnetic resonance imaging was 6.7 cm (range 3.5-11.0 cm). Histologically, 20 patients had squamous cell carcinoma and 9 had adenocarcinoma. C-ion RT was performed as a dose-escalation study in the initial trials. All patients received prophylactic whole-pelvic or extended-field irradiation and local boost. The total dose to the cervical tumor was 52.8-74.4 Gy (relative biological effectiveness) in 20 or 24 fractions. Weekly cisplatin (40 mg/m(2)/week, five cycles) was concurrently given to four patients. The median follow-up of all patients was 28.6 months (range 8.8-238.6 months). Grade 2 or higher late complications in the bladder were observed in eight patients, with seven developing vesicovaginal fistula. Six patients had Grade 2 or higher complications in the rectosigmoid colon. The 3-year overall survival rate was 47%, the 3-year local control rate was 66%, and the 3-year disease-free survival rate was 28%. In this study, C-ion RT showed favorable local control with reasonable toxicities, but the results were still unsatisfactory. We have the expectation of improvement of therapeutic effects by using C-ion RT with concurrent chemotherapy.	bladder
Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer.	Tumor cell-derived hyaluronidase HYAL-1 degrades hyaluronic acid (HA) into angiogenic fragments (AGF: 10-12 disaccharides). AGF support tumor growth and progression. Urine and tissue HAase/HYAL-1 levels are sensitive markers for high-grade bladder cancer (BCa) and its metastasis. In preclinical models of BCa, we evaluated whether o-sulfated AGF (sHA-F) inhibits HAase activity and has antitumor activity. At IC50 for HAase activity inhibition (5-20 μg/ml [0.4-1.7 μM]), sHA-F significantly inhibited proliferation, motility and invasion of HYAL-1 expressing BCa cells (253J-Lung, HT1376, UMUC-3), P<0.001. sHA-F did not affect the growth of HYAL-1 non-expressing BCa (5637, RT4, T24, TCCSUP) and normal urothelial (Urotsa, SV-HUC1) cells. sHA-F treatment induced apoptosis by death receptor pathway. sHA-F downregulated transcript and/or protein levels of HA receptors (CD44, RHAMM), p-AKT, β-catenin, pβ-Catenin(S552), Snail and Twist but increased levels of pβ-Catenin(T41/S45), pGSK-3α/β(S21/S9) and E-cadherin. sHA-F also inhibited CD44/Phosphoinositide 3-kinase (PI-3K) complex formation and PI-3K activity. AGF addition or myristoylated-AKT overexpression attenuated sHA-F effects. Contrarily, HYAL-1 expression sensitized RT4 cells to sHA-F treatment. In the 253J-L and HT1376 xenograft models, sHA-F treatment significantly inhibited tumor growth (P<0.001), plausibly by inhibiting angiogenesis and HA receptor-PI-3K/AKT signaling. This study delineates that sHA-F targets tumor-associated HA-HAase system and could be potentially useful in BCa treatment.	bladder
BCG-osis following intravesical BCG treatment leading to miliary pulmonary nodules, penile granulomas and a mycotic aortic aneurysm.	A 69-year-old male patient who was treated with intravesical BCG for carcinoma in situ of the bladder, went on to develop systemic features of BCG-osis. This diagnosis was supported by significant radiological and clinical findings. These systemic features include pulmonary miliary lesions, a mycotic abdominal aortic aneurysm and penile lesions. Owing to a breakdown in the relationship between the patient and the National Health Service, the patient has declined BCG treatment. This case highlights the potential rare side effects of intravesical BCG treatment and the risk associated with non-treatment of BCG-osis.	bladder
Insignificant role of bacillus Calmette-Guérin maintenance therapy after complete transurethral resection of bladder tumor for intermediate- and high-risk non-muscle-invasive bladder cancer: Results from a randomized trial.	OBJECTIVES: To investigate the effect of bacillus Calmette-Guérin maintenance therapy on patients with intermediate- and high-risk non-muscle-invasive bladder cancer receiving aggressive complete transurethral resection of bladder tumors standardized by well-trained surgeons. METHODS: A total of 95 patients were prospectively enrolled. Patients were diagnosed with multiple or recurrent non-muscle-invasive bladder cancer (Ta and T1), or with carcinoma in situ after complete transurethral resection of bladder tumors. Patients with Ta or T1 tumors without carcinoma in situ received six bacillus Calmette-Guérin instillations as induction therapy. Those with carcinoma in situ underwent eight bacillus Calmette-Guérin instillations as induction therapy. The patients were randomized into maintenance and non-maintenance groups. The maintenance group received intravesical bacillus Calmette-Guérin instillations once a week for 3 weeks at 3, 6, 12 and 18 months after bacillus Calmette-Guérin instillation. The primary end-point was recurrence-free survival. RESULTS: A total of 88 patients were evaluated. The average follow-up period was 48.3 ± 19.0 months. Five-year recurrence-free survival rates for the maintenance and non-maintenance groups were 80.1% and 79.3%, respectively. Five-year progression-free survival rates of the maintenance and non-maintenance groups were 92.4% and 85.3%, respectively. Recurrence- and progression-free survival rates did not significantly increase in the maintenance group compared with that in the non-maintenance group. CONCLUSIONS: Bacillus Calmette-Guérin maintenance therapy did not improve recurrence- and progression-free survival rates after the initial complete transurethral resection of bladder tumors compared with that after bacillus Calmette-Guérin induction therapy alone.	bladder
Molecular Subtypes of Non-muscle Invasive Bladder Cancer.	In this issue of Cancer Cell, Hedegaard et al. report a comprehensive multi-center transcriptional analysis of non-muscle invasive urothelial bladder cancer. They describe three molecular subtypes similar to those seen in other cohorts, as well as a unique CIS signature associated with risk of progression to muscle invasive cancer.	bladder
Functional inhibition of Hsp70 by Pifithrin-μ switches Gambogic acid induced caspase dependent cell death to caspase independent cell death in human bladder cancer cells.	Heat shock protein-70kDa (Hsp70) is a member of molecular chaperone family, involved in the proper folding of various proteins. Hsp70 is important for tumor cell survival and is also reported to be involved in enhancing the drug resistance of various cancer types. Hsp70 controls apoptosis both upstream and downstream of the mitochondria by regulating the mitochondrial membrane permeabilization (MMP) and apoptosome formation respectively. In the present study, we have elucidated the role of Hsp70 in Gambogic acid (GA) induced apoptosis in bladder cancer cells. We observed that functional inhibition of Hsp70 by Pifithrin-μ switches GA induced caspase dependent (apoptotic) cell death to caspase independent cell death. However, this cell death was not essentially necrotic in nature, as shown by the observations like intact plasma membranes, cytochrome-c release and no significant effect on nuclear condensation/fragmentation. Inhibition of Hsp70 by Pifithrin-μ shows differential effect on MMP. GA induced MMP and cytochrome-c release was inhibited by Pifithrin-μ at 12h but enhanced at 24h. Pifithrin-μ also reverted back GA inhibited autophagy which resulted in the degradation of accumulated ubiquitinated proteins. Our results demonstrate that Hsp70 plays an important role in GA induced apoptosis by regulating caspase activation. Therefore, inhibition of Hsp70 may hamper with the caspase dependent apoptotic pathways induced by most anti-cancer drugs and reduce their efficacy. However, the combination therapy with Pifithrin-μ may be particularly useful in targeting apoptotic resistant cancer cells as Pifithrin-μ may initiate alternative cell death program in these resistant cells.	bladder
miR-130b, an onco-miRNA in bladder cancer, is directly regulated by NF-κB and sustains NF-κB activation by decreasing Cylindromatosis expression.	Persistent activation of NF-κB signaling is closely related to chronic inflammation and tumorigenesis. Commonly, NF-κB signaling is tightly controlled by multiple feedback loops and regulators, such as the deubiquitinases (DUBs). However, in cancer cells, NF-κB may override these feedbacks through special pathways and lead to the sustained activation. In the present study, we demonstrate that in transitional cell carcinoma (TCC) of bladder, miR-130b plays an oncogenesis role, it enhanced proliferation, invasion and migration of TCC cell, and was highly correlated with tumor progression. On the other hand, NF-κB directly regulated the transcription of miR-130b by binding with its promoter region. Importantly, we verify that, through deceasing the expression of Cylindromatosis (CYLD), a K63-specific DUB and endogenous blocker of NF-κB signaling, miR-130b can in return sustain the persistent activation of NF-κB, which may promote the malignant progression of TCC. Thus, the present study uncovers a potential signaling transduction in which NF-κB is continuously activated, and may provide a novel therapeutic approach for the clinical management of TCC.	bladder
Perioperative evaluation of respiratory impedance using the forced oscillation technique: a prospective observational study.	BACKGROUND: Intravascular fluid shifts, mechanical ventilation and inhalational anesthetic drugs may contribute to intraoperative lung injury. This prospective observational study measured the changes in respiratory impedance resulting from inhalational anesthesia and mechanical ventilation in adults undergoing transurethral resection of bladder tumors. The components of respiratory impedance (resistance and reactance) were measured using the forced oscillation technique (FOT). METHODS: Respiratory resistance at 5 Hz (R5) and 20 Hz (R20), respiratory reactance at 5 Hz (X5), resonant frequency (Fres) and area of low reactance (ALX) were measured before and immediately after surgery in 30 adults. In addition, preoperative vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1.0) were evaluated using spirometry. All patients were intubated with an endotracheal tube and were mechanically ventilated, with anesthesia maintained with sevoflurane. Pre- and postoperative FOT measurements were compared using Wilcoxon paired rank tests, and the relationships between FOT measurements and preoperative spirometry findings were determined by Spearman's rank correlation analysis. RESULTS: Twenty-six patients were included in the final analysis: postoperative FOT could not be performed in four because of postoperative restlessness or nausea. The mean duration of surgery was 47 min. All components of respiratory resistance deteriorated significantly over the course of surgery, with median increases in R5, R20, and R5-R20 of 1.67 cmH2O/L/s (p < 0.0001), 1.28 cmH2O/L/s (p < 0.0001) and 0.46 cmH2O/L/s (p = 0.0004), respectively. The components of respiratory reactance also deteriorated significantly, with X5 decreasing 1.7 cmH2O/L/s (p < 0.0001), Fres increasing 5.57 Hz (p < 0.0001) and ALX increasing 10.51 cmH2O/L/s (p < 0.0001). There were statistically significant and directly proportional relationships between pre- and postoperative X5 and %VC, %FEV1.0 and %FVC, with inverse relationships between pre- and postoperative Fres and ALX. CONCLUSIONS: All components measured by FOT deteriorated significantly after a relatively short period of general anesthesia and mechanical ventilation. All components of resistance increased. Of the reactance components, X5 decreased and Fres and ALX increased. Pre- and postoperative respiratory reactance correlated with parameters measured by spirometry. TRIAL REGISTRATION: JMA-IIA00136 .	bladder
Improvements in the Treatment of Patients Suffering from Bladder-Prostate Rhabdomyosarcoma: A Report from the CWS-2002P Trial.	PURPOSE: Modern treatment concepts for bladder/prostate rhabdomyosarcoma (BPRMS) are designed to improve survival, to reduce therapy intensity, and to increase bladder preservation rates. Nevertheless, treatment is not optimal. The purpose of this study was to analyze BPRMS patients treated within the CWS-2002P trial regarding outcome, treatment modalities, complications, and to compare the data with the precursor trial CWS-96. METHODS: Fifty children with localized embryonal BPRMS were analyzed. Eight patients were excluded. Patients received neoadjuvant chemotherapy. At week 9, reassessment using MRI scan was performed. Depending on tumor size, age, and response, local therapy consisting of radiotherapy and/or surgery was initiated. After local therapy, systemic therapy was continued. RESULTS: Patients' median age was 35.6 months. Median follow-up was 59 months. The 5-year OS was 84.5 % and the 5-year ES 79.9 %. Ten patients underwent combined radiochemotherapy and tumor resection (5-year ES: 87.5 %). Six patients were treated solely with radiochemotherapy (5-year ES: 60 %). Twenty-six patients received preoperative chemotherapy followed by tumor resection (ES: 80.8). One patient was treated with chemotherapy only and survived. The bladder preservation rate was 80.9 %. CONCLUSIONS: The outcome within the CWS-2002P trial regarding OS and ES seemed to be better than in the precursor trial CWS-96 due to a reduction of protocol violations, but there was no statistical significant difference possibly due to low numbers. Radiotherapy was used less frequently, and the bladder preservation rate was slightly higher. Novel concepts will be required in the future to improve bladder preservation rates.	bladder
Both cancerous miR-21 and stromal miR-21 in urothelial carcinoma are related to tumour progression.	AIMS: Urothelial carcinoma (UC) is a globally common cancer. miR-21 appears to be important in the tumorigenesis of almost all types of human cancer. However, its precise localization and significance in UC have yet to be clarified. The aim of this study was to examine miR-21 expression in UC and reveal its clinicopathological importance. METHODS AND RESULTS: Tissue arrays of 232 UCs were examined for miR-21 by the use of in-situ hybridization. One hundred and forty-eight transurethral resection specimens and 84 surgically resected specimens were used. After miR-21 positivity had been evaluated separately in tumour cells and the tumour stroma, it was compared with clinicopathological factors and overall survival. miR-21 was strongly expressed in tumour cells in 9% of cases and in the tumour stroma in 6% of cases. Stromal miR-21 positivity was lower than that of cancerous miR-21. Both miR-21s were correlated with each other and related to tumour stage, locus, and histological grade. In addition, strong positivity of miR-21 in cancer and the stroma was significantly related to poorer prognosis among surgically resected cases. In a Cox proportional hazard model, cancerous miR-21 was the only independent prognostic factor except for tumour stage. CONCLUSIONS: miR-21 in both cancer and stromal cells is closely related to tumour progression in UC. miR-21 may be a prognostic marker for cancer progression.	bladder